title: Quercitylcinnamates, a new series of antidiabetic bioconjugates possessing α-glucosidase inhibition and antioxidant.
abstract: Antidiabetic agents possessing dual functions, α-glucosidase inhibition and antioxidant, have been accepted to be more useful than currently used antidiabetic drugs because they not only suppress hyperglycemia but also prevent risk of complications. Herein, we design antidiabetic bioconjugates comprising of (+)-proto-quercitol as a glucomimic and cinnamic analogs as antioxidant moieties. Fifteen quercitylcinnamates were synthesized by direct coupling through ester bond in the presence of DCC and DMAP. Particular quercityl esters 6a, 7a and 8a selectively inhibited rat intestinal maltase and sucrose 4-6 times more potently than their parents 6, 7 and 8. Of synthesized bioconjugates, 6a was the most potent inhibitor against maltase and sucrose with IC₅₀ values of 5.31 and 43.65 μM, respectively. Of interest, its inhibitory potency toward maltase was 6 times greater than its parent, caffeic acid (6), while its radical scavenging (SC₅₀ 0.11 mM) was comparable to that of commercial antioxidant BHA. Subsequent investigation on mechanism underlying inhibitory effect of 6a indicated that it blocked maltase and sucrose functions by mixed inhibition through competitive and noncompetitive manners.
authors.affiliation: Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Eakkaphon
authors.initials: E
authors.lastname: Rattanangkool
authors.forename: Preecha
authors.initials: P
authors.lastname: Kittikhunnatham
authors.forename: Thanakorn
authors.initials: T
authors.lastname: Damsud
authors.forename: Sumrit
authors.initials: S
authors.lastname: Wacharasindhu
authors.forename: Preecha
authors.initials: P
authors.lastname: Phuwapraisirisan
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007422:Intestines / Q000201:enzymology; D010851:Picrates / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D001713:Biphenyl Compounds; D002934:Cinnamates; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl; D005947:Glucose
keywords: Caffeic acid; Diabetes mellitus; Glucosidase; Multifunctional drug; Quercitol